Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple factors have been hypothesized over the last century to be causative or contributory for Parkinson's disease. Hereditary factors have recently emerged as a major focus of Parkinson's disease research. Until recently most of the research on the etiology of Parkinson's disease concentrated on environmental factors, and the possibility that genetic factors contribute significantly to the pathogenesis of Parkinson's disease has been neglected. However, it has become increasingly apparent that even in sporadic cases, the disease most likely reflects a combination of genetic susceptibility and an unknown environmental insult. Moreover, the identification of genes and proteins that may cause hereditary parkinsonism substantially contributes to our ability to understand the pathogenesis of Parkinson's disease and may help in the early identification of the disease and its treatment. The discovery of alpha-synuclein mutations in families with autosomal dominant Parkinson's disease sheds light on its role in sporadic Parkinson's disease. It seems that this protein tends to aggregate when the cellular milieu is altered [14-16]. The question as to the exact changes that cause its deposition remains open. One of the major possibilities is oxidative stress [16]. The role of these aggregates in neuronal cell death is also still unclear. Transgenic mice expressing wild-type human alpha-synuclein developed progressive accumulation of alpha-synuclein and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus and the substantia nigra. These alterations were associated with loss of dopaminergic terminals and motor impairments [24]. This finding suggests that accumulation of alpha-synuclein may play a causal role in sporadic Parkinson's disease as well. The parkin protein seems to be a crucial survival factor for nigral neurons [15]. The parkin protein is related to the ubiquitin pathway, which is important in the elimination of damaged proteins. Ubiquitin-mediated degradation of proteins plays a central role in the control of numerous processes, including signal transduction, receptor and transcriptional regulations, programmed cell death, and breakdown of abnormal proteins that may interfere with normal cell functions. Further studies on the function of Parkin protein and its relation to the ubiquitin pathway could elucidate at least one of the molecular mechanisms of nigral neuronal death. A mutation in the ubiquitin carboxy-teminal hydrolase L1 gene also implies the importance of the ubiquitin pathway in Parkinson's disease. Abnormal tau protein was found to be the cause of familial frontotemporal dementia and parkinsonism. It tends to form filamentous structures, which may lead to neuronal death. Elucidation of the molecular mechanism of neuronal death in this disease may contribute to our understanding of sporadic diseases with tau accumulation, such as corticobasal degeneration, progressive supranuclear palsy, Pick's disease, Alzheimer's disease and possibly also the pathogenesis of Parkinson's disease. Other genetic loci have been identified by linkage analysis of patients with familial parkinsonism. These loci conceal other genes and proteins that may be pivotal factors in the pathogenesis of Parkinson's disease. The discovery of genetic mutations in patients with parkinsonism may offer us new insights into the understanding of the pathways leading to neuronal death and development of Parkinson's disease. It may also help in the early identification of susceptible people to this disease and possibly in developing new treatment strategies.
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PMID:Heredity in Parkinson's disease: new findings. 1143 38

Increasing evidence indicates that the dysfunction of ubiquitin-proteasome system (UPS) is associated with Alzheimer's disease (AD). In the ubiquitin-proteasome pathway, Ubiquitin Carboxy-terminal Hydrolase-L1 (UCH-L1) plays an important role for the cellular clearance of abnormal proteins. Since a substitution of serine by tyrosine at codon 18, exon 3 (S18Y polymorphism) of the UCH-L1 gene exhibits a protective effect against the development of degenerative disease such as sporadic Parkinson's disease (PD) in several different ethnic groups, we hypothesized that UCH-L1 gene S18Y polymorphism may have that same effect on the pathologic process of AD. We examined UCH-L1 S18Y polymorphism genotypes of 116 sporadic AD patients and 123 healthy subjects in Chinese Han population using PCR-restriction fragment length polymorphism (RFLP) analysis. The allele and genotype data as well as data after stratification by age of onset failed to demonstrate any association between AD and S18Y polymorphism. However, after stratification by gender, female AD patients showed significantly less frequencies of Y allele and YY genotype in S18Y polymorphism than female controls (P = 0.003 and P = 0.015 respectively). We conclude that Y allele and YY genotype of S18Y in the UCH-L1 gene may have a protective effect against sporadic AD in female subjects, probably due to altering the function of UCH-L1 and the interactions among different risk factors.
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PMID:Genetic association between Ubiquitin Carboxy-terminal Hydrolase-L1 gene S18Y polymorphism and sporadic Alzheimer's disease in a Chinese Han population. 1662 67